Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors.
ADP-ribosylation
COVID-19
SARS-CoV-2
drug discovery and development
macrodomain
non-structural protein 3 (NSP3)
virtual screening
Journal
Pathogens (Basel, Switzerland)
ISSN: 2076-0817
Titre abrégé: Pathogens
Pays: Switzerland
ID NLM: 101596317
Informations de publication
Date de publication:
15 Feb 2023
15 Feb 2023
Historique:
received:
12
01
2023
revised:
03
02
2023
accepted:
10
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
26
2
2023
Statut:
epublish
Résumé
The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire that was identified as a potential target for the development of antiviral agents, due to its critical role in viral replication and consequent pathogenicity in the host. By combining virtual and biophysical screening efforts, we discovered several experimental small molecules and FDA-approved drugs as inhibitors of the NSP3 macrodomain. Analogue characterisation of the hit matter and crystallographic studies confirming binding modes, including that of the antibiotic compound aztreonam, to the active site of the macrodomain provide valuable structure-activity relationship information that support current approaches and open up new avenues for NSP3 macrodomain inhibitor development.
Identifiants
pubmed: 36839595
pii: pathogens12020324
doi: 10.3390/pathogens12020324
pmc: PMC9965906
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R007195/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210634
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 223107
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/W016613/1
Pays : United Kingdom
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